Determinants of vaccine adherence among non-dialysis chronic kidney disease patients in Qatar

Introduction: Chronic kidney disease (CKD) is a global health problem. Reduced innate and adaptive immunological responses predispose CKD patients to infections. Despite the clinical and epidemiological importance of CKD and the great value of vaccination as a prophylactic measure, the utilization of recommended vaccines in Qatar has not yet been evaluated. Methods: We conducted a cross-sectional study to estimate the level of influenza, pneumococcal, and hepatitis B vaccination and the predictors of adherence to these recommended vaccines among non-dialysis CKD patients receiving renal ambulatory care in Qatar from 1 September 2020 to 30 April 2021. Complete vaccination was defined as receiving the three vaccines, and partial vaccination was defined as receiving one or two vaccines. The full and partial vaccination predictors were assessed using multivariate logistic regression and reported as odds ratio (OR) with p<0.05 indicating statistical significance. Results: 416 non-dialysis CKD patients were included in our analysis. 73% were males; the mean age was 56 ± 15 years. More than 50% of the patients were from the Middle East, followed by 36% from Asia. Most patients had concurrent hypertension, concurrent diabetes mellitus, and were stage V CKD. Only 12% of the patients were fully vaccinated, while 73% received partial vaccination. The predictors of vaccination included age, gender, Asian origin, employment, living conditions, concurrent medical conditions, CKD stage, allergy to medications, and use of injectable medications. Only stage V CKD positively predicted adherence to full and partial vaccinations in non-dialysis CKD patients. Conclusion: There is very low adherence to the recommended vaccines in CKD patients, with a prevalence of complete vaccination of 12% only. Increased public awareness about the importance of vaccination in CKD may improve the adherence rates among these patients in Qatar.


INTRODUCTION
Chronic kidney disease (CKD) is a global health problem, as the number of patients with end-stage renal disease (ESRD) in the United States has increased from approximately 10,000 in 1973 to around 700,000 in 2015. 1 Worldwide prevalence of CKD was estimated to be 10.4% among men and 11.8% among women, with higher rates in low and middle-income countries. 2Moreover, the yearly incidence of CKD was estimated to be around 1700 per million, according to a cohort study of a 5.5-year follow-up period (study population base of 405,000). 3ecreased kidney function is established when the glomerular filtration rate is below 60 mL/min/1.73m 2 .This state is defined as chronic kidney disease (CKD) only if it is persistent for at least three months so that it can be distinguished from Acute Kidney Injury (AKI).Urine albumin excretion of more than 30 mg/day is another criterion that indicates kidney damage and has to be persistent for at least three months too. 4 Repeating these tests is essential to evaluate chronicity and for patients with test results near the threshold values. 5taging chronic kidney disease is critical to effectively manage the case, predict and prevent possible complications, and delay the disease progression.Staging involves three main aspects: the cause of the disease, the GFR (glomerular filtration rate) stage, and the albuminuria stage. 4igh morbidity and high demand for health care services are observed in both non-dialysis and dialysis CKD patients. 6The rate of hospitalization was around double among dialysis patients in comparison to early-stage CKD patients. 7egarding disability-adjusted life years (DALYs), the Determinants of vaccine adherence among non-dialysis chronic kidney disease patients in Qatar September 1, 2020, and April 30, 2021, and who met the inclusion criteria were included in this study.The total number of patients inquired about in the study was 416.

Objectives
Primary objective: To report adherence to recommended vaccinations (Hepatitis B, pneumococcal, and influenza) among non-dialysis CKD patients.Secondary objective: To determine the predictors of receiving the recommended vaccinations (Hepatitis B, pneumococcal, and influenza vaccinations) among non-dialysis CKD patients using patientand disease-related factors.

Inclusion and Exclusion Criteria
We included patients older than 18 who are diagnosed with CKD (all-stage CKD patients except for patients on dialysis).We excluded patients who had had kidney transplantation, were on dialysis, or had a severe adverse or hypersensitive response to vaccines.

Measurements and Outcomes
The computerized patient files were checked, and information was taken for two sections: (1) demographic factors, including age, gender, nationality, occupation, housing conditions, the existence of chronic illnesses other than CKD, the stage of renal disease, the presence of allergies, the number of chronic medications, and the presence of injectable chronic medications.(2) the status of Hepatitis B, pneumococcal, and influenza vaccinations.Evaluated outcomes were the prevalence of complete vaccination, defined as receiving the three vaccines, and the majority of partial vaccination, defined as receiving one or two vaccines.The outcomes were reported as percentages, along with full and partial vaccination predictors.

Data Analysis
Data were analyzed using a statistical package for the social sciences (SPSS) version 28.0 software (IBM Corporation Armonk, New York, USA).For descriptive statistics, we used the mean and standard deviation, or the median and interquartile range, depending on the distribution of variables.For categorical data, we utilized percentages wherever they were relevant.Percentages were provided for the prevalence of both full and partial vaccination.Multivariate logistic regression was used to assess the full and partial vaccination predictors.The results were given as odds ratios (OR), with a p-value of < 0.05 representing statistical significance.Tests were done at a 2-sided 5% level of significance.The work was done in line with the Strengthening the reporting of observational studies in epidemiology (STROBE) statement.

Ethical Consideration
The Institutional Review Board at Hamad Medical Corporation approved the study, IRB register number MRC-01-21-530.Due to the retrospective nature of data collection and analysis, a waiver for the requirement to get informed consent was granted.

RESULTS
A total of 416 patients with CKD were included in our retrospective analysis.Around three-quarters of the patients were males (73%), and the mean age was 56 ± 15 years, as demonstrated in (Table 1).More than 50% of the patients were from the Middle East, followed by 36% from Asia.Around 77% of the patients lived with their families, while 21% lived with roommates.Most patients had concurrent hypertension, stage V CKD, and diabetes mellitus (96%, 77%, and 64%, respectively).More than 75% of patients had CKD stage V and 20% had CKD stage IV.The vast majority of the patients (91%) had polypharmacy with more than five medications.Only 12% of the patients were fully vaccinated.In comparison, 73% received partial vaccination, as shown in (Table 2).More than half of the patients received pneumococcal vaccine and hepatitis B vaccine, 54% and 52%, respectively.In comparison, only 26% received the influenza vaccine as part of renal ambulatory care.
VOL. 2023 / ART.33   Determinants of vaccine adherence among non-dialysis chronic kidney disease patients in Qatar Determinants of vaccine adherence among non-dialysis chronic kidney disease patients in Qatar vaccinated.In comparison, 73% received partial vaccination, and stage V CKD was a positive predictor of adhering to complete vaccination and partial vaccination in CKD.The gender disparity in our study is close to that in Qatar in general. 17he importance of these vaccines emerges from the fact that innate and adaptive immunological responses are affected by chronic kidney disease, so CKD patients are more susceptible to infections and decreased effectiveness of vaccines.The B and CD4+ T lymphocytes are declining, and the response to antigens is reduced.More importantly, there is an inadequacy in the production of antibodies after vaccination due to impairment in monocyte functions.−22 Furthermore, impairment of the immune system can be attributed to additional factors such as uremia, mineral disorders, and inflammation that are present in almost all late CKD patients. 23ecause of the different epidemiological priorities, there is no optimal global immunization policy for CKD patients, which results in varied vaccination regimes across countries. 10eople with chronic illnesses generally have a lower tendency to receive the recommended vaccines than expected, even after ensuring their safety and huge beneficence. 24The Hepatitis B vaccine reduces the risk of infection by around 70 percent, and health status can be predicted by the patient's response to vaccination in terms of seroconversion. 25,26The pneumococcal vaccine is highly recommended, 27 given that Streptococcus pneumoniae is the most pneumonia-causing agent among CKD patients, 28 and since it has a poor prognosis and higher mortality rate 27 .Annual Influenza vaccine is also recommended despite the limited evidence on its efficacy in CKD patients in particular. 29he prevalence of receiving the full recommended vaccines in our population under study is low, which might indicate that non-dialysis patients are not interested in getting these vaccines.The least received vaccine was the influenza vaccine, which could be because it is an annual vaccine.

DISCUSSION
In our institution, all dialysis patients receive the complete recommended vaccines before starting the dialysis regimen.However, it remains unclear whether the non-dialysis CKD receives the most important, widely agreed upon vaccines for Hepatitis B, Influenza, and Pneumococcal. 16In this cross-sectional study, only 12% were fully  Determinants of vaccine adherence among non-dialysis chronic kidney disease patients in Qatar them, and offering health promotion sessions is essential. 35Patients of low educational/ socioeconomic status should be provided more focus as studies showed generally lower vaccination rates among these groups. 36nfortunately, given its secondary data nature, we did not examine this variable in our research.Educational activities regarding the importance of vaccination have been proven effective during the COVID-19 era in Qatar, 37 so it is one of the recommended interventions to improve vaccination rates among CKD patients.Generally speaking, it is recommended that family physicians and specialists periodically check the vaccination status of their patients when encountered.Also, vaccination campaigns screen patients' electronic records and phone patients who are not vaccinated to advise them on the process, benefits, and free vaccines.
This study was an observational study that has its limitations.First, due to the study's retrospective nature, there was a risk of missing data.Second, the retrospective nature prevented acquiring information directly from the patients, which would have allowed us to investigate personal reasons for not taking the recommended vaccines and the opportunity to know whether patients had already taken the vaccine from other healthcare providers such as the private sector, or in their home country so it was not recorded in the system.Third, the study review period was during the COVID-19 era, which might have underestimated vaccination prevalence as attending ambulatory clinic appointments was not optimal due to COVID-19 safety measures.Nevertheless, in this study, we explored the rate of recommended vaccination among the vulnerable group of non-dialysis CKD patients, who might be overlooked compared to dialysis patients.Special vaccination attention is required for older patients and early-stage CKD patients as part of the mission to achieve The Global Vaccine Action Plan (GVAP), which focuses on the goal of life without vaccine-preventable illnesses for all communities. 38

CONCLUSIONS
Our study demonstrated low adherence to the recommended vaccines in non-dialysis CKD patients, with a prevalence of only 12%.Awareness of vaccination in CKD patients' needs to be reemphasized in some settings, or simply that patients do not know about the need or availability of vaccines. 24A study showed that one reason for non-adherence toward Hepatitis B vaccination was the limited discussion between patients and their physicians regarding its benefits.Also, vaccination appointments should be of importance as well. 30he COVID-19 pandemic made the focus of CKD patients on receiving COVID-19 vaccines rather than other vaccines.Moreover, the COVID-19 pandemic forced many clinics to remain closed to the public for physical visits, and they were instead only providing telephone consultations, which may have affected the vaccine uptake rate.The COVID-19 situation has created many challenges to the health system in Qatar, especially in the hemodialysis department, where patients must have their sessions regularly. 31Many measures were taken to overcome these issues, such as designating a dialysis unit for COVID-19 patients, implementing a screening questionnaire to assess patients' health status, and performing a rapid antigen test to identify COVID-19 cases. 32he presence of Diabetes Mellitus seems to encourage CKD patients to seek Influenza vaccination, as they receive more health educational materials, and they usually have more follow-up visits.Stage V CKD was the most potent positive predictor for all vaccines, and these patients may be more flexible in accepting vaccination compared to early stages of CKD, who may not recognize the importance of these vaccines. 33Also, in our institution, these patients are being followed up more frequently and are more likely to receive more health education materials in general.
We did not find any negative predictors for Pneumococcal and Influenza vaccines.Yet, the older ages and history of allergy to oral medications were associated with lower Hepatitis B vaccine uptake.It could be because older patients usually need more explanation and information regarding the vaccine's safety and the possibility of not completing the three doses we considered not vaccinated.The 2-dose Hepatitis B vaccine could be a solution, and it has demonstrated high efficacy and cost-effectiveness 34 and could promote better adherence.
A systematic review showed that to improve vaccination coverage, educating patients, tracking

Table 1 . Baseline characteristics of patients with chronic kidney disease receiving renal ambulatory care (N = 416)
*Reported as mean ± standard deviation; CKD: chronic kidney disease

Table 2 . Prevalence of vaccination among patients with chronic kidney disease receiving renal ambulatory care (N = 416)
VOL. 2023 / ART.33Determinants of vaccine adherence among non-dialysis chronic kidney disease patients in Qatar